本文選題：激光散斑成像　切入點(diǎn)：腦血流　出處：《華中科技大學(xué)》2014年博士論文　論文類型：學(xué)位論文

【摘要】：目的：激光散斑成像是近年興起的一種活體成像技術(shù),用于觀察活體組織內(nèi)的血流,而如何運(yùn)用于腦血管病的研究還存在醫(yī)學(xué)轉(zhuǎn)化的實(shí)際困難。本論文采用激光散斑成像技術(shù)觀察小鼠腦血流量和腦血流改變情況下側(cè)支循環(huán)情況,結(jié)合小鼠的光化學(xué)腦缺血模型和標(biāo)準(zhǔn)化方法用于動(dòng)態(tài)、連續(xù)監(jiān)測缺血灶模型的信號(hào)改變規(guī)律。進(jìn)一步分析血流信號(hào)改變與腦組織病理變化相互關(guān)系,探索光化學(xué)模型的神經(jīng)血管的變化規(guī)律。以驗(yàn)證光化學(xué)腦缺血模型激光散斑成像成為一種高效的藥物篩查方法的可能性。 方法：利用激光散斑成像系統(tǒng)觀察C57/BL6小鼠的腦皮層血流圖,通過結(jié)扎單側(cè)頸動(dòng)脈的方法觀察小鼠側(cè)支循環(huán)形成情況。通過不同激光劑量進(jìn)行小鼠腦光化學(xué)造模,探索不同劑量激光造模的效果與特點(diǎn)。分析腦皮層缺血區(qū)域血流信號(hào)的改變與小鼠腦梗塞體積、小血管數(shù)量的關(guān)系。免疫熒光檢測小血管的變化規(guī)律及以小血管為中心的神經(jīng)細(xì)胞、膠質(zhì)細(xì)胞的變化規(guī)律。采用激光散斑成像技術(shù)驗(yàn)證尤瑞克林、米諾環(huán)素、地塞米松的對光化學(xué)腦缺血模型的作用。 結(jié)果：激光散斑成像實(shí)現(xiàn)C57小鼠動(dòng)態(tài)的腦皮層血流檢查,C57小鼠進(jìn)行光化學(xué)腦缺血造模后可以進(jìn)行多次重復(fù)性檢查。不同劑量激光造模造成的光化學(xué)缺血灶病理改變具有不同特點(diǎn)。光化學(xué)缺血區(qū)域標(biāo)準(zhǔn)化的SrCBF (Standardized Regional Cerebral Blood Flow)與缺血組織體積呈負(fù)相關(guān)關(guān)系,相關(guān)系數(shù)R2為0.9001；標(biāo)準(zhǔn)化的SrCBF變化趨勢與缺血區(qū)域小血管的單位面積百分比變化趨勢類似。病理結(jié)果顯示化學(xué)模型的缺血區(qū)域在1d內(nèi)仍有Neun陽性細(xì)胞；28d發(fā)現(xiàn)在缺血邊緣發(fā)現(xiàn)極少量的Neun陽性及Brdu陽性的細(xì)胞。通過GFAP染色,可以發(fā)現(xiàn)在光化學(xué)缺血性腦缺血模型的缺血灶的邊緣區(qū)可以發(fā)現(xiàn)星形膠質(zhì)細(xì)胞的活化,5d時(shí)星形細(xì)胞活化達(dá)到頂峰,活化的星形細(xì)胞與小血管關(guān)系密切。在光化學(xué)模型的藥物篩查實(shí)驗(yàn)中,手術(shù)后3d收集比較小鼠皮層的興趣區(qū)的SrCBF,米諾環(huán)素組的局部血流量和腦缺血組織體積與對照組比較具有統(tǒng)計(jì)學(xué)差異。 結(jié)論：激光散斑成像系統(tǒng)能夠?qū)崟r(shí)動(dòng)態(tài)的顯示腦血流的變化,這為小鼠腦皮層小血管功能和腦缺血的側(cè)支循環(huán)相關(guān)研究提供了良好的研究工具。不同劑量的光化學(xué)造模可以制作出不同程度的缺血梗塞灶,適合不同類型實(shí)驗(yàn)的研究需要。通過激光散斑成像的標(biāo)準(zhǔn)化的SrCBF可以作為血流量的指標(biāo),可用于評價(jià)不同小鼠的血流恢復(fù)程度,一定程度上反映小鼠的光化學(xué)缺血灶的缺血組織體積大小,提示局部小血管的數(shù)量。光化學(xué)腦缺血模型中,小血管與神經(jīng)細(xì)胞、星形膠質(zhì)細(xì)胞具有緊密關(guān)系。激光散斑成像系統(tǒng)光化學(xué)腦缺血模型檢驗(yàn)?zāi)X缺血后的藥物治療效果具有一定可靠性和高效性,米諾環(huán)素等抗炎、血管保護(hù)藥物可能有益于相關(guān)疾病的治療。
[Abstract]:Objective: laser speckle imaging is a living imaging technique developed in recent years, which is used to observe the blood flow in living tissue. In this paper, we used laser speckle imaging technique to observe the cerebral blood flow and the change of cerebral blood flow in mice. In combination with the photochemical cerebral ischemia model of mice and the standardized method, the signal changes of the ischemic focal model were continuously monitored, and the relationship between the changes of blood flow signal and the pathological changes of brain tissue was further analyzed. In order to verify the possibility of laser speckle imaging of photochemical cerebral ischemia model as an effective drug screening method, the changes of nerve and blood vessels in photochemical model were investigated. Methods: the cerebral cortex blood flow of C57 / BL6 mice was observed by laser speckle imaging system. The formation of collateral circulation was observed by ligation of unilateral carotid artery. To explore the effects and characteristics of laser modeling with different doses, to analyze the changes of blood flow signal in cerebral ischemic region and the volume of cerebral infarction in mice. The relationship between the number of small blood vessels, the changes of small blood vessels by immunofluorescence, and the changes of nerve cells and glial cells with small vessels as the center. Eureklin and minocycline were verified by laser speckle imaging. Effect of dexamethasone on photochemical cerebral ischemia model. Results: dynamic cerebral cortical blood flow examination in C57 mice was achieved by laser speckle imaging. After photochemical cerebral ischemia model was made in C57 mice, repeated examinations could be carried out. Pathology of photochemical ischemic foci caused by laser modeling with different doses. The changes have different characteristics. There is a negative correlation between the volume of ischemic tissue and the standardized Regional Cerebral Blood flow in photochemical ischemic region. The correlation coefficient R2 was 0.9001; the change trend of standardized SrCBF was similar to that of the percentage change of unit area of small vessels in ischemic region. Pathological results showed that there were still Neun positive cells in ischemic region within 1 day and 28 days after ischemia. A very small number of Neun and Brdu positive cells were found on the edges. It can be found that the activation of astrocytes peaked at 5 days after photochemical ischemic cerebral ischemia in the marginal region of ischemic foci. Activated astrocytes are closely associated with small blood vessels. In the photochemical model of drug screening, Three days after operation, the SrCBF of cortical area of interest, the regional blood flow and the volume of cerebral ischemic tissue in minocycline group were compared with those in the control group. Conclusion: laser speckle imaging system can display the changes of cerebral blood flow in real time. This provides a good tool for the study of cortical microvascular function and collateral circulation of cerebral ischemia in mice. Different doses of photochemical models can be used to make different ischemic infarct areas. Standardized SrCBF by laser speckle imaging can be used as an index of blood flow and can be used to evaluate the degree of blood flow recovery in different mice. To some extent, it reflects the volume of ischemic tissue in mice with photochemical ischemia, indicating the number of local small vessels. In the model of photochemical cerebral ischemia, small vessels and nerve cells, There is a close relationship between astrocytes. The photochemical cerebral ischemia model of laser speckle imaging system has a certain reliability and high efficiency in detecting the effect of drug therapy after cerebral ischemia, such as minocycline, etc. Vascular protection drugs may be beneficial to the treatment of related diseases.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R743.3

【共引文獻(xiàn)】

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